Ph.D. survival: is a jack of all trades a master of none?

Over the years science has changed a great deal. In just the last 50 years or so we’ve seen a major revolution in scientific research, due primarily to our understanding of DNA and ultimately how it codes for protein. But there have been quite a few changes even in the 12 or 13 years since I received my Ph.D. One of these changes, which I would like to address in this blog, relates to the way that science is done. More specifically, the way in which science is done by today’s Ph.D. students.

I hope, dear reader, that you will not already have tired of my reminiscences of what it was like when I was a Ph.D. student. If you have, I suggest you either logout now, or take a deep breath and read on.

If you got this far, then either curiosity got the better of you, or you haven’t read too many of my blogs. In any event, as a Ph.D. student in the 1990s, I was expected to master various techniques in the course of my studies. In my case, it was a combination of some work with mice, a lot of protein biochemistry, and some very standard and basic sub-cloning techniques. I spent an awful lot of time working on different types of two dimensional gel electrophoresis; in other words separating proteins both by size (molecular weight) and by charge, or alternatively by size and whether or not the proteins were linked by disulfide bonds.

As a principal investigator now, and a mentor of graduate students, I see that things have changed considerably. The students of today need to utilize many more techniques than I did in order to progress. It is not uncommon for a student who is versed in biochemical techniques to also have to learn various physiological/cell biological assays that might be outside his/her “comfort zone”. A lot of this has to do with the ‘globalization of science’, and the arrival of the kits on the scene.

These kits are both a blessing and a curse. On the one hand, they really do allow students to rapidly employ a huge arsenal of techniques that simply would not be possible without a simplified ready-to-use system available. On the other hand, it appears that many students–perhaps anxious to take advantage of these kits as quickly as possible–do not really make an attempt to understand the science behind them.

Unfortunately, this has led in some cases to students who are basically “buying science”. What I mean by this is that some of the most fundamental and important elements in the students’ scientific education are being lost. For example, I’ve come across students who have performed one of the most basic cell biology/biochemistry experiments–the immunoprecipitation of proteins with antibodies–with such kits. For those who are not familiar, this is a very basic technique where one uses a specific antibody to pull down and precipitate a specific protein from a cell lysate.

For those lacking experience with this basic technique, these kits are perceived as an easy way out. They contain pre-prepared lysis buffer to break up the cells and make a lysate from which the immunoprecipitation can be done. Instructions are given, but the rationale for each step is lacking. The problem is that there really isn’t a “one-size-fits-all” lysis buffer and system for immunoprecipitation. The concentration of salt can be critical, as can the choice of detergent used to make micelles from the membranes, as well as a host of other factors that can also be of importance. I find that some of the students have absolutely no clue what’s contained within these magic buffers, and of course this precludes any possibility of troubleshooting, should the experiment not succeed. So the rapid progress that can be attained with pre-prepared kits and solutions comes with a price–students who are no longer masters of their own research.

But is it all really bad? Not necessarily. If students and researchers are aware of these potential pitfalls, and at least stay technically conversant with some of the most fundamental techniques used, then the age of the kits can actually propel research forward quite rapidly.

A PI and his students become almost like a child in a candy store; all the techniques are available–one only needs money to pay for them. In fact, this has become the age of outsourcing in science. When I began my Ph.D., researchers were still carrying out cumbersome DNA sequencing reactions in their own laboratories. Today, no scientist worth his/her salt (sorry, another awful pun) would waste time doing this. It’s all sent out to companies or sequencing facilities at the university itself.

So, one possibility is that laboratories will decline in size over time. The researchers; PI, postdocs and Ph.D. students will all need to spend more time thinking, more time reading, more time figuring out which new assays will be applicable to the research; how to best spend the money to get “the most research for the buck.” There will be less work at the bench, and more thought given to which kits to order and what work to outsource and to whom.

Is this a scary scenario? I don’t necessarily see it that way; I think that as long as researchers maintain a firm grasp key number of scientific techniques, it’s probably a good development for science. The better students adapt and learn, and the better mentors ensure that their students understand the technical concepts of the science that they carry out. After all, many of us scientists firmly believe that critical thinking is the key component of graduate education. And there’s no reason that this element should be lessened in the new age of science.

How about some “Yays and nays” from the other side of the pond?

About Steve Caplan

I am a Professor of Biochemistry and Molecular Biology at the University of Nebraska Medical Center in Omaha, Nebraska where I mentor a group of about 10 students, postdoctoral fellows and researchers working on endocytic protein trafficking. My first lablit novel, "Matter Over Mind," is about a biomedical researcher seeking tenure and struggling to overcome the consequences of growing up with a parent suffering from bipolar disorder. Lablit novel #2, "Welcome Home, Sir," published by Anaphora Literary Press, deals with a hypochondriac principal investigator whose service in the army and post-traumatic stress disorder actually prepare him well for academic, but not personal success. Novel #3, "A Degree of Betrayal," is an academic murder mystery that is now in press! All views expressed are my own, of course--after all, I hate advertising.
http://www.stevecaplan.net

13 Responses to Ph.D. survival: is a jack of all trades a master of none?

Most of the kits in our lab come with detailed scientific discussion, theory and diagrams in their appendices. I’ve never seen a kit booklet without one – are you really finding instructions with no explanation or context? That’s really bad practice by the companies, I’d say. But of course the students would still need to read these appendices.

I’m of two minds here. I make a lot of my own solutions, but I also use kits. Yet even when I use solutions I make myself – let’s use RIPA (for the above mentioned immunoprecipitation assay) as an example – it doesn’t necessarily mean I need to know the chemistry behind it. I make it following a recipe that was passed down from post-doc to post-doc over many years. It usually works, but if it didn’t, I’d have to go to the literature to work out why. I know the general idea – what the salt and detergent is for – but I wouldn’t say my knowledge is anything other than superficial. Most of the tried and true recipes are tried and true precisely because they do tend to work under a wide range of conditions. As long as I know HOW to troubleshoot in the event my conditions aren’t in that range, I’m not too fussed about delving too deeply. Perhaps that makes me a lazy scientist – I’m not really sure!

Actually, quite a number of these kits resort to the “proprietary” excuse, although you are right, that many others do contain scientific explanations that are better than “mix A with B, and then wait 5 min.”

Funny you bring up RIPA buffer–you must be a mind reader! That’s exactly an example I was thinking of. I was sitting on a student supervisory committee some time ago, and listening to explanations of about why he was unable to co-immunoprecipitate 2 proteins (and I mean the positive controls, that are known and have been documented to interact). I started to get technical, because the student had been trying for months. In this example, the student had no idea that different buffers COULD be used, or even generally that salt and detergent make a difference. He did not know that SDS is a component of RIPA buffer, and that this would likely make it almost impossible to maintain interactions with other precipitated proteins.

So, that’s my concern. Your case is very different, as you obviously: 1) understand the fundamentals, and 2) know where to look and what to do if things aren’t working

I don’t think we should try to turn back the clock, and I really believe that there’s no way for today’s scientists to maintain a deep level of understanding of the multiple techniques they will encounter–yet at the same time, I think there is concern that those behind the curve will end up unable to do even the most basic troubleshooting.

I agree that understanding the techniques are essential for doing good science – otherwise you don’t know what you have done or the flaws of it (cause there is always a lot of flaws). Myself, as a computational biologist, never use the wet lab what so ever, and am of the view that kits or self made solutions are as much science as hard drives and computer programs are. These are just the tools – you need to be sufficiently good in using then in order to do research. But the true science is knowing what you want to do and figuring out how to get there. And that can not be done without understanding the tools at some decent level.

The analogy I always use is that I don’t really know exactly how my car works, but I know how to drive it, how to put fuel in it and how to change a tyre. The same goes for my electron microscope (only it doesn’t have tyres), and the same goes for the kits I used to use as a PhD/postdoc, and even the techniques I use now in EM prep. For example, there is a tecnique we use called high pressure freezing which is followed by freeze substitution. The freeze sub cocktails and the time and temperature regimes are myriad. Some last for over a week, some 24 hours. The samples are so precious and expensive to produce, and the technique so time and labour intensive, that people generally find a “general protocol” and stick to it quasi religiously. Only if it doesn’t work will they try something else, and even then may give up after a couple of attempts simply as there are so many other things to try they couldn’t possibly try them all.

I agree with your point about outsourcing. Our little EM unit here operates in precisely that way, otherwise our EM users really would be whistling in the dark a bit without us as specialists. It allows them to concentrate on their system and that picture, whilst we help them properly plan, execute and analyse their EM correctly. I think it works well, and emphasises that science should be teamwork, not an individual pursuit.

I fully agree, Ian. As you point out, though, there is a necessity for understanding some bare minimum–such as how to chnge tires or check your engine oil, etc.

For anyone doing subcloning/molecular biology, the fine points of DNA sequencing are largely useless–it’s a means to an end. But I do think that researchers need to have a basic understanding of how it works (of course a historical perspective of how the method was originally discovered and later evolved certainly builds a student’s critical thinking.

I am not sure whether anyone is still following this thread, but I think there is another fundamental problem with using too many kits and/or outsourcing that Steve touched only slightly. It all comes down to plain old money. When I did my PhD (which I did in a very well funded lab, so I never had to worry about spending a bit more on another fancy kit), I spent a couple of months in the lab of a collaborator, who, it turned out, was not as well funded. Suddenly, I had to pull out all the old protocols how to do a mini-prep without a kit, etc. It was fun in the beginning and turned out to be quite a nuisance after a while… Anyhow, the point I want to make: A little while into my stint in that collaborator*s group, a new postdc joined their lab. After a week or so he had the first protein sample ready for an SDS-PAGE and Western. Trouble was as he said (quote): ¨I have never cast a gel in my life before. I had a technician do that for me in my old lab.” The rest of us (incredulously):”You had your own technician as a PhD student?!?” He: “Yes of course, we all did?”
So it goes to show that the chap (probably due to no fault of his own) got into a situation where he suddenly couldn*t do basic science anymore, just because he went from a rich to a “poorer” lab (as I have no doubts scores of young scientists do all the time).
But what were to become of someone like him (or me, another victim of the comforts of a well-funded lab) if (when, hopefully) we have to set up our first independent lab, on our first grant and realize: “My, I*m poor!!!” ???

Good points. I’m assuming, though, that a well-trained researcher should be able to get a technique like SDS PAGE up and running pretty quickly–even if he or she never actually poured a gel before. Having a technician do ALL of the students’ wet-work does sound like overkill, though…